More than 100,000 people with MS are being treated with ocrelizumab worldwide. New analysis shows that drug exposure and low B-cell levels reduce the risk of progression. Long-term data advise early initiation of therapy.
Ocrelizumab reduces the risk of multiple sclerosis progression. This was demonstrated by safety data presented by Hoffmann-La Roche at the 71st Annual Meeting of the Academy of Neurology (AAN) in Philadelphia.
Ocrelizumab is a humanized monoclonal antibody that selectively binds to the B lymphocyte antigen CD20, leading to elimination of affected CD20-positive B cells. These are suspected to be significantly involved in the damage of myelin sheath and axons. Because ocrelizumab binds only to CD20 surface antigens expressed on certain B cells but not on stem or plasma cells, important immune system functions are preserved during treatment. The compound, available under the trade name Ocrevus®, is the only therapy approved to date for relapsing-remitting MS (RMS) and primary progressive MS (PPMS).
Ocrelizumab is administered as an intravenous infusion every six months. Initially, 2× 300 mg are administered at intervals of two weeks. Subsequent doses are 600 mg.
Safe even at higher exposure
The new safety data come from 4501 patients with relapsing or primary progressive multiple sclerosis, for a combined total of 12,599 patient-years on ocrelizumab. They show a correlation between a higher drug concentration and lower B-cell levels as well as lower progression rates. Thus, 24 weeks of therapy in RMS patients reduced the risk of progression across all exposure levels compared with interferon beta-1a – this with increasing ocrelizumab exposure. The situation was similar in patients with PPMS. Administration of the agent resulted in a reduced risk of disease progression confirmed over 24 weeks for all exposure levels in the placebo comparison. Under therapy with ocrelizumab, T1 gadolinium-enhancing lesions and new or enlarging T2 lesions were no longer detectable on MRI. Annual relapse rates were also lowered: RMS patients relapsed at a low level (0.13-0.18) across all exposure ranges.
Higher ocrelizumab exposure did not result in increased adverse events. Stephen Hauser is pleased with this favorable risk-benefit profile, which has been confirmed in all clinical studies. These are the first data to demonstrate that higher Ocrevus® exposure is associated with better progression control without compromising safety, according to the head of the OPERA trials scientific committee, director of the Weill Institute for Neuroscience and chief of the Department of Neurology at the University of California.
Continued reduction in the risk of progression
Long-term data from the open-label Phase III extension studies OPERA and ORATORIO in RMS and PPMS are also positive. For a study period of more than five years, they demonstrate that early treatment with ocrelizumab significantly reduces the risk of ongoing disease progression – with a sustained effect. This was shown, for example, in the OPERA extension study: In the group of patients who received ocrelizumab for the entire observation period of five years, the proportion of RMS patients with disease progression confirmed over 48 weeks was lower than in the group that was switched to ocrelizumab only after two years of treatment with interferon beta-1a (10.4% vs. 15.7%; p=0.004). In the ORATORIO trial, the proportion of PPMS patients with disease progression confirmed over 48 weeks was also lower in the group that had received ocrelizumab continuously for five and a half years compared to patients who were switched from placebo to ocrelizumab after the 120-week double-blind phase (43.7% vs. 53.1%; p=0.03).
1-year results from the Phase III OBOE (Ocrelizumab Biomarker Outcome Evaluation) study demonstrated that with the use of ocrelizumab, the concentration of a biomarker of neuronal inflammation in serum and cerebrospinal fluid decreased in RMS patients at 12, 24, and 52 weeks.
Source: Hoffmann-LaRoche
InFo NEUROLOGY & PSYCHIATRY 2019; 17(4): 36.
